The anatomy of appetite
What actually is appetite? And why do some people become severely obese while others are able to maintain a stable weight without effort? Jennifer Trent Staves talks to two researchers in the field to digest the topic
Eat to live: it sounds simple. The digestive system runs from the mouth, down the oesophagus to our stomach and intestines, where food is absorbed for energy or the waste material passed.
But a look around at the various body shapes, different palates and increasing waistlines of the global population implies that something much more subtle is at work. According to World Health Organization (WHO) figures, globally in 2014 more than 1.9 billion adults (39 per cent) were overweight and more than 600 million (13 per cent) were obese, with 41 million children under the age of 5 being overweight or obese too. And, WHO fears, these figures are likely to increase in future, as while the problem is concentrated in high-income countries, low- and middle-income countries are beginning to experience the crisis as well.
“We have a sophisticated system for controlling our appetite and our weight,” explains Dr Sadaf Farooqi, Wellcome Trust Senior Clinical Fellow at the University of Cambridge, “and appetite is really the body’s system for what we eat and how we eat. What we prefer to eat.”
This sophisticated system involves not only the gut but also the brain and is influenced by our genetic make-up and environment. The way in which these parts work, separately and together, and how to optimise them for an ideal appetite is the focus of intense research by Farooqi and other researchers.
The gut is at the core of understanding appetite, as the image of a full belly after a meal attests. The stomach, pancreas and intestines are key players, secreting hormones to tell you to eat more or less. When you are hungry, your stomach will produce ghrelin, a hormone that encourages you to eat more. Or, once you’ve eaten enough, the pancreas will secrete insulin, which tells your body to eat less. These are just two of the potent cocktail of hormones that, in theory, tailor our appetite.
The concept of being full – or satiated – is an important one in appetite research. “Satiety is actually lack of appetite and follows eating,” says Professor Steve Bloom of Hammersmith Hospital, Imperial College London. He has been one of the first recipients of Wellcome’s Seeding Drug Discovery awards, which focus on finding molecules that can be developed into drugs.
“In our research, having found that there were specific hormones which switched off appetite, we wanted to make them useful for controlling appetite in people who are trying to control their weight,” he explains.
Using these hormones to help reduce appetite is the focus of Bloom and his research team’s work: “When you see people suffering from obesity, really trying to lose weight, suffering from nasty diseases that are a consequence of being overweight, you want to help them.”
“That’s why my team works on an appetite-reduction medication. If we succeed in our research, we should be able to make obesity a thing of the past,” he says.
The gut may produce these hormones, but it’s the brain that interprets the signals. Bloom says: “If we want to control appetite, we have to look both at the gut and at the brain. It’s the gut that tells the brain to stop eating, but it’s the brain that does the stopping.”
The control centre for appetite is the brain, agrees Farooqi. “It will govern how you eat and how much energy you burn up, on a day-to-day basis and over a long period of time. The brain pulls in things you see, smell, taste, hear.” The brain, like the gut, produces its own hormones both to encourage and inhibit appetite. The hormones MCH and NPY, which are produced by the hypothalamus, can block pain signals, such as a feeling of fullness, and encourage eating. The hypothalamus also secretes melanocyte-stimulating hormones, which can slow down appetite.
But there is still much to understand about the brain, as it is not simply a straightforward mechanism for passing signals along. “Our brain also pulls in things you’ve learnt about to determine how we eat and what we eat,” explains Farooqi. So personal memories of food, both good and bad, and emotions around eating that are individual to a person, are stored in the brain. How these influences affect appetite are yet to be completely understood.
The gut and brain may be working in tandem to control appetite, but our genetic make-up is crucial to whether this appetite is healthy.
In some cases, eating too much – and consequently obesity – cannot be controlled by the person alone.
“We know that for all of us, regardless of our body weight, whether we’re slim, overweight or severely obese, 40–70 per cent of our weight is determined by genetic factors,” explains Farooqi. “It determines the weight that we end up at, in a given environment.”
She and her team are working with a cohort of over 3,500 children to understand the causes of severe obesity where conventional methods of understanding and treating obesity have been unsuccessful.
Many of these children were unable to stop eating through any usual method – and either the children themselves, or their parents, were blamed for ‘causing’ the obesity. Farooqi has even seen families subjected to child protection orders.
Her team has been able to find new genes, mutations and variants which are affecting appetite.
“In one case finding a gene has already led to a new treatment. This disorder is called leptin deficiency and the lack of this gene results in a lack of a hormone called leptin in the blood, which then should normally control your appetite.” Giving these children injections of leptin has seen their body weight plummet.
“Finding these genes has allowed us to intervene from a medical point of view and get some of these children off the child protection register.”
But the leptin gene is one of hundreds or perhaps thousands involved in appetite, and she wants to track down the other genes that could be responsible for insatiability: “We’ve found a lot of genes over the last ten years, but there are an awful lot more to find.” Indeed, in her cohort, only 8 per cent of patients have a form of obesity that has – to date – been explained.
Obesity, back in prehistoric times or even up to 30 years ago, wasn’t the epidemic it is today. But if our brains, our guts and our genes haven’t altered significantly in the last three decades, what’s responsible for the rise in appetite?
The food that we’re eating has changed. Not only is our food more processed and higher-calorie, it is also easier to access than ever before, which is affecting the other factors involved in appetite.
“Food is more easily available, cheaply available, and the kind of food we now eat has more calories than say 30–50 years ago. Even if you are slim and have a normal appetite, the number of calories you’re taking in is probably more than your mother may have taken in,” explains Farooqi.
“We’re a species who’ve overcome a lot of famines. In the times of hunter-gatherers, every four or five years, a third of the population would die of famine, so it was really necessary to grab that last crust of bread and stuff your mouth, so to speak,” says Bloom.
“We’re intrinsically wanting to eat all the time because any minute, there might be another famine. And also if you didn’t eat in the middle of the summer, you might not survive the winter. We have an appetite too big for our needs in a civilised society where there’s a supermarket at every corner.”
Both Bloom and Farooqi agree that environment works with our genes and can’t act alone. “People who are obese have a genetic propensity to eat too much. But they won’t eat too much if there isn’t plenty of food available,” Bloom adds.
He advocates controlling the outside problem with a medication to suit our environment: “If the present approach to treatment of appetite works well – which I think it will – obesity will become a thing of the past.”
But in a constantly changing environment there are still questions left to answer. “There are really important questions out there about what’s in the food that may be making us feel more hungry, or more full,” says Farooqi. “Certain types of food seem to make you feel more hungry. And that’s a really major challenge that we don’t yet fully understand.”
- Gastrointestinal hormones regulating appetite (2006)
- The regulation of appetite (2006)
- Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity (2008)
- Human obesity: a heritable neurobehavioral disorder that is highly sensitive to environmental conditions (2008)
- WHO figures on obesity